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Nigrostriatal dopaminergic activities in dementia with Lewy bodies in relation to neuroleptic sensitivity: Comparisons with Parkinson's disease

Lookup NU author(s): Dr Margaret Piggott, Emeritus Professor Elaine Perry, Dr Elizabeth Marshall, Professor Ian McKeith, Mary Johnson, Heather Melrose, Dr Jennifer Court, Stephen Lloyd, Dr Andrew Fairbairn, Andrew Brown, Paul Thompson, Emeritus Professor Robert Perry

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Abstract

Background: In dementia with Lewy bodies (DLB) mild extrapyramidal symptoms are associated with moderate reductions in substantia nigra neuron density and concentration of striatal dopamine. Many DLB patients treated with typical neuroleptics suffer severe adverse reactions, which result in decreased survival. Methods: In a series of DLB cases, with and without neuroleptic sensitivity, substantia nigra neuron densities, striatal dopamine and homovanillic acid concentrations, and autoradiographic [H-3]mazindol and [H-3]raclopride binding (to the dopamine transporter and D2 receptor, respectively) were analyzed and compared to control and idiopathic Parkinson's disease cases. Results: D2 receptors were up-regulated in neuroleptic-tolerant DLB and Parkinson's disease compared to DLB without neuroleptic exposure and controls. D2 receptors were not up-regulated in DLB cases with severe neuroleptic reactions, Dopamine uptake sites were reduced concomitantly with substantia nigra neuron density in Parkinson's disease compared to controls, but there was no significant correlation between substantia nigra neuron density and [H-3]mazindol binding in DLB groups. There was no significant difference in substantia nigra neuron density, [H-3]mazindol binding, and dopamine or homovanillic acid concentration between neuroleptic-tolerant and -sensitive groups. Conclusions: Failure to up-regulate, D2 receptors in response to neuroleptic blockade or reduced dopaminergic innervation may be the critical factor responsible for neuroleptic sensitivity. Biol Psychiatry 1998;44: 765-774 (C) 1998 Society of Biological Psychiatry.


Publication metadata

Author(s): Melrose HL; McKeith IG; Piggott MA; Marshall EF; Thompson P; Fairbairn A; Perry RH; Perry EK; Johnson M; Court JA; Lloyd S; Brown A

Publication type: Article

Publication status: Published

Journal: Biological Psychiatry

Year: 1998

Volume: 44

Issue: 8

Pages: 765-774

Print publication date: 01/10/1998

ISSN (print): 0006-3223

ISSN (electronic): 1873-2402

Publisher: Elsevier Inc.

URL: http://dx.doi.org/10.1016/S0006-3223(98)00127-9

DOI: 10.1016/S0006-3223(98)00127-9


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